Bimanual mirror-symmetrical movement (MSM) is relatively easy to control movement. Different MSM tasks may have different activations and interhemispheric interactions. The purpose of this study is to compare anatomo-physiological features such as hemispheric activations and dominance of two different MSMs, namely melody-playing and rhythm. We examined functional MRI (fMRI) recordings in a group of fifteen right-handed pianists performing two separate tasks: bimanual rhythm and bimanual melody-playing on two different keyboards with standard key order for right hand and reversed for left hand, which allows homolog fingers’ movements. Activations and laterality indices on fMRI were examined. The results show that significant cerebellar activations (especially in anterior cerebellum) in both groups. Significant primary sensorimotor cortical activations are observed in the melody-playing group. While there are also bilaterally symmetric activations, and laterality indices suggest overall lateralization towards the left hemisphere in both groups. Activations in the left fronto-parietal cortex, left putamen and left thalamus in conjunction with right cerebellar activations suggest that the left cortico-thalamo-cerebellar loop may be a dominant loop. Dynamic causal modeling (DCM) indicates the presence of causal influences from the left to the right cerebral cortex. In conclusion, melody-playing with bimanual MSM is a complex in-phase task and may help activate the bilateral cortical areas, and left hemisphere is dominant according to laterality indices and DCM results. On the other hand, bimanual rhythm is a simpler in-phase task and may help activate subcortical areas, which might be independent of the voluntary cortical task.